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Solid Tumor, AdultPhase 1/2NCT05597839

Study of DF9001 in Patients With Advanced Solid Tumors

A Phase 1/2 study testing DF9001 and KEYTRUDA® (pembrolizumab) in people with Solid Tumor, Adult, run by Dragonfly Therapeutics at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

DF9001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells. The study will occur in two phases. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Adult
What is being tested?
DF9001 and KEYTRUDA® (pembrolizumab)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
17 sitesUnited States
Study dates
15 Nov 2022to 15 Aug 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent.
  • Male or female patients aged ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry and an estimated life expectancy of at least 3 months.
  • Adequate hematological function per protocol.
  • Adequate hepatic function per protocol.
  • Adequate renal function per protocol.
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  • Participation in the use of contraception during the study, and for 150 days after the last dose of study drug for women of child-bearing potential (WOCBP) and 30 days after the last dose of study drug for male patients, as defined by the Clinical Trial Facilitation Group (CTFG) guidelines.
  • Histologically proven locally advanced or metastatic solid tumors of epithelial origin that (1) have squamous NSCLC or HNSCC, (2) has documented EGFR protein expression or EGFR amplification or polysomy in their medical history from previous testing, or (3) test positive for EGFR expression via archival or fresh biopsy tissue prior to study enrollment using a validated immunohistochemistry (IHC) assay.
  • Evidence of objective disease, but participation does not require a measurable lesion.
  • Inclusion Criteria: Head and Neck Squamous Cell Carcinoma (HNSCC) Expansion Cohorts
  • Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
  • Histologically documented relapsed or metastatic HNSCC. Primary tumor locations include oropharynx, oral cavity, hypopharynx, or larynx. Patients may not have a primary tumor site of nasopharynx (any histology).
  • Patients must have radiographic disease progression while on or after having received both platinum-based or fluoropyrimidine-based chemotherapy and an anti-PD-(L)1 therapy, administered either concurrent or sequentially.
  • Willing and able to provide the most recently available tissue blocks representing tumor biopsy obtained prior to treatment initiation. If recent tissue is not available, then a newly obtained baseline biopsy of an accessible tumor is required. Note that "recent" is defined as no intervening systemic anticancer therapies from the time of the last treatment of the prior therapy until screening for this trial.
  • Willing to undergo on-treatment biopsies, if safe and medically feasible.
  • Inclusion Criteria: Renal Cell Carcinoma (RCC) Expansion Cohorts
  • Patients must have radiographic progression during treatment or after completing treatment for advanced (recurrent/unresectable/metastatic) disease or be intolerant to prior therapy.
  • Histologically documented relapsed or metastatic RCC that has documented EGFR expression or EGFR gene amplification or polysomy in their medical history from previous testing or test positive for EGFR expression (Section 6.2 EGFR Positivity) via archival (only if a block is available) or fresh biopsy tissue prior to study enrollment using a validated IHC assay. Cytology specimens cannot be used for the purpose of defining EGFR expression to meet eligibility.
  • Patients with clear cell RCC (ccRCC) must have radiographic progression after receipt of one of the following combination regimens as the preceding line of therapy:
  • PD-1/PD-L1-targeting mAb with or without a VEGFR-TKI.
  • PD-1-targeting mAb with a CTLA-4 monoclonal.
  • Patients with non-clear cell RCC (nccRCC) are not required to have received prior therapy in the metastatic setting.
  • Patients with RCC in general are not required to have received TKI therapy (eg, axitinib, cabozantinib, lenvatinib + everolimus, tivozanib).
  • Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
  • Willing and able to provide the most recently available tissue blocks representing tumor biopsy obtained prior to treatment initiation. If recent tissue is not available, then a newly obtained baseline biopsy of an accessible tumor is required. Note that "recent" is defined as no intervening systemic anticancer therapies from the time of the last treatment of the prior therapy until screening for this trial.
  • Willing to undergo on-treatment biopsies, if safe and medically feasible.
  • Inclusion Criteria: Non-Small Cell Lung Cancer (NSCLC) Expansion Cohorts
  • Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IIIC, or stage IV NSCLC disease with or without actionable genomic alterations (AGA) (per the 7th IASLC classification of NSCLC), or recurrent disease.
  • Patients with squamous NSCLC do not require EGFR testing as part of this study to be eligible.
  • Non-squamous NSCLC patients who have documented EGFR expression or EGFR gene amplification or polysomy in their medical history from previous testing or test positive for EGFR expression (Section 6.2 EGFR Positivity) via archival (only if a block is available) or fresh biopsy tissue prior to study enrollment using a validated IHC assay.
  • Patients with stage IIIB or IIIC must be ineligible for local therapies with curative intent (eg, radiotherapy or surgery).
  • Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
  • Patients must have recurrent or progressive disease during or after first line combination therapy with checkpoint inhibitors and platinum-based chemotherapy OR must have recurrent or progressive disease within 6 months after completing platinum- based chemotherapy for local disease, including those with actionable genetic alterations. They must not have received any subsequent lines of therapy.
  • Status for actionable mutations (EGFR, ALK, ROS1, RET, etc.) must be known (when testing is available as per country/region standard of care practices); patients with actionable mutations must have received and progressed on, have been intolerant to, or not be a candidate for standard TKIs (as available per country/region standard of care practices).
  • Willing and able to provide the most recently available tissue blocks representing tumor biopsy obtained prior to treatment initiation. If recent tissue is not available, then a newly obtained baseline biopsy of an accessible tumor is required. Note that "recent" is defined as no intervening systemic anticancer therapies from the time of the last treatment of the prior therapy until screening for this trial.
  • Willing to undergo on-treatment biopsies, if safe and medically feasible.

Who cannot join

  • Patients must not have had chemotherapy, radiotherapy (other than palliative bone- directed radiotherapy, as described in in exclusion criterion #2), or major surgery, or received another investigational agent within 28 days or 5 half-lives of the drug (if known), whichever is shorter, before the start of study treatment.
  • Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids.
  • Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system (CNS) disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
  • Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [except for palliative bone-directed radiotherapy, which is not a target lesion], immune therapy, or cytokine therapy [except for erythropoietin]), major surgery (excluding prior diagnostic biopsy), concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days or 5 half-lives of the drug (if known), whichever is shorter, before the start of study treatment. Short-term administration of systemic steroids (eg, for allergic reactions or the management of irAEs) is allowed. Note: Patients receiving bisphosphonate or denosumab are eligible, provided treatment was initiated at least 14 days before the first dose of DF9001.
  • Previous malignant disease other than the target malignancy to be investigated in this study within the last 3 years. Exceptions (eg, basal or squamous cell carcinoma of the skin, or cervical carcinoma in situ) can be considered on a case-by-case basis, in consultation with the Medical Monitor.
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  • Life expectancy of less than 6 months.
  • Receipt of any organ transplantation, including autologous or allogeneic stem-cell transplantation.
  • Significant acute or chronic infections (including historic positive test for human immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C tested during the screening window). If HBsAg is negative and the anti-hepatitis B core antibody is positive, then hepatitis B viral DNA load must be undetectable.
  • Preexisting autoimmune disease (except for patients with vitiligo) needing treatment with systemic immunosuppressive agents for more than 28 days within the last 3 years, or clinically relevant immunodeficiencies (eg, dysgammaglobulinemia or congenital immunodeficiencies). Patients with a history of immune-related endocrinopathies (eg, hypothyroidism, type 1 diabetes mellitus [TIDM], and adrenal insufficiency) that are stable on hormone replacement therapy may be eligible for this study.
  • Patients with a known medical history that may place them at risk of known toxicities of EGFR blockade.
  • History of or ongoing keratitis, ulcerative keratitis, or corneal perforation.
  • History of cardiopulmonary arrest unless this was caused by an acute, reversible etiology that is no longer present.
  • History of or ongoing pulmonary fibrosis or interstitial lung disease.
  • Known severe hypersensitivity reactions to mAbs (≥ Grade 3 of the NCI-CTCAE v5.0), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly controlled asthma).
  • Persisting toxicity related to prior therapy >Grade 1 NCI-CTCAE v5.0; however, alopecia ≤Grade 2, endocrinopathies ≤Grade 2, and sensory neuropathy ≤ Grade 2 is acceptable.
  • Patients who have received an anti-PD-(L)1 as a previous line of therapy that have experienced either of the following:
  • a Grade 3 or Grade 4 drug-related toxicity.
  • a Grade 2 drug-related toxicity that impacted either the lungs, cardiac, or the nervous system, caused by the administration of the anti-PD-(L)1.
  • Received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.
  • A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines are allowed.
  • Pregnancy or lactation in females during the study.
  • Known alcohol or drug abuse.
  • Serious cardiac illness or medical conditions, including but not limited to:
  • History of New York Heart Association class III or IV heart failure or systolic dysfunction (left ventricular ejection fraction [LVEF] <55%).
  • High-risk uncontrolled arrhythmias (eg, tachycardia with a heart rate >100/min at rest).
  • Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular (AV) block (eg, AV-block, second degree AV block Type 2 [Mobitz 2], or third-degree AV-block).
  • Angina pectoris requiring anti-anginal medication.
  • Clinically significant valvular heart disease.
  • Evidence of transmural infarction on electrocardiograms (ECGs).
  • Poorly controlled hypertension (defined as systolic >160 mm Hg or diastolic >100 mm Hg).
  • Clinically relevant uncontrolled cardiac risk factors, clinically relevant pulmonary disease, or any clinically relevant medical condition in the opinion of the Investigator that may limit participation in this study.
  • Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
  • All other significant diseases (eg, inflammatory bowel disease), which, in the opinion of the Investigator, might impair the patient's ability to participate.
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
  • Legal incapacity or limited legal capacity.
  • Incapable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
  • Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study treatment (for NSCLC cohorts only).
  • Patients with brain metastases, unless all of the following criteria are met:
  • CNS lesions are asymptomatic, previously treated and no active therapy is required (ie, no corticosteroids for edema),
  • Radiologically stable (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention.
  • Imaging demonstrates stability of disease 28 days from last treatment for CNS metastases.
  • Active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
  • Patients with leptomeningeal disease are excluded.
  • History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Active infection requiring systemic therapy.
  • Severe hypersensitivity (≥Grade 3) to pembrolizumab, and/or any of its excipients.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Cincinnati

    Cincinnati, Ohio, 45219

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • Banner MD Anderson

    Gilbert, Arizona, 85234

  • UC Irvine Medical Center

    Irvine, California, 92617

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • AMR Kansas City

    Kansas City, Missouri, 64114

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Louisville Hospital

    Louisville, Kentucky, 40202

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Rutgers

    New Brunswick, New Jersey, 08903

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • UMPC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Mayo Clinic Minnesota

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Phase 1/1b First-In-Human, Multi-Part, Open-Label Study to Investigate the Safety, Tolerability, Pharmacokinetics, Biological, and Clinical Activity of DF9001 as a Monotherapy and in Combination Therapies in Patients With Advanced (Unresectable, Recurrent, or Metastatic) Solid Tumors, and Expansion in Selected Indications

DF9001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell activation signals to specific receptors on cancer cells. The study will occur in two phases. The first phase will be a dose escalation phase, enrolling patients with various types of solid tumors that express epidermal growth factor receptor (EGFR). The second phase will include a dose expansion using the best dose selected from the first phase of the study. Multiple cohorts will be opened with eligible patients having selected solid tumors (monotherapy and in combination with pembrolizumab).

Being tested
DF9001, KEYTRUDA® (pembrolizumab)
Keywords
EGFR, NK Cell, Immunotherapy, Non-Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, Renal Cell Carcinoma, pembrolizumab, KEYTRUDA®
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DF9001Drug

    Immunotherapy agent targeting NK cells.

  • KEYTRUDA® (pembrolizumab)Drug

    Anti-PD-1 immunotherapy agent

Study groups in NCT05597839
Study groupRoleWhat they receive
Monotherapy DF9001 Dose EscalationExperimentalDose escalation cohorts of DF9001 in sequential ascending order.
Receives: Drug: DF9001
Monotherapy DF9001 Expansion in Head and Neck Squamous Cell CarcinomaExperimentalMonotherapy expansion cohort enrolling up to 20-40 patients with head and neck squamous cell carcinoma (HNSCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.
Receives: Drug: DF9001
Monotherapy DF9001 Expansion in Non-small Cell Lung CancerExperimentalMonotherapy expansion cohort enrolling up to 20-40 patients with Non-small cell lung cancer (NSCLC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.
Receives: Drug: DF9001
Combination Expansion of DF9001 and pembrolizumab in Head and Neck Squamous Cell CarcinomaExperimentalCombination expansion cohort using DF9001 and a PD-1 checkpoint inhibitor enrolling 20-40 patients with head and neck squamous cell carcinoma (HNSCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.
Receives: Drug: DF9001; Drug: KEYTRUDA® (pembrolizumab)
Combination Expansion of DF9001 and pembrolizumab in Renal Cell CarcinomaExperimentalCombination expansion cohort using DF9001 and a PD-1 checkpoint inhibitor enrolling 20-40 patients with renal cell carcinoma (RCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.
Receives: Drug: DF9001; Drug: KEYTRUDA® (pembrolizumab)
Monotherapy DF9001 Expansion in Renal Cell CarcinomaExperimentalMonotherapy expansion cohort enrolling up to 20-40 patients with renal cell carcinoma (RCC) using the recommended phase 1b dose (REED) identified in the Monotherapy Dose Escalation arm.
Receives: Drug: DF9001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number, severity, and duration of treatment-related adverse events (TRAEs) according to NCI-CTCAE v5.0.

    To assess the safety of DF9001 by measuring Number of subjects with Treatment-Related Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

    Measured: Screening visit up to 28 days after last treatment on the study.

  2. Number of patients with AEs and TRAEs.

    To assess the safety of DF9001 by measuring Number of subjects with Treatment-Related Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

    Measured: Screening visit up to 28 days after last treatment on the study.

  3. Assessment of number of dose limiting toxicities experienced on study as defined per criteria in the study protocol

    To assess the number of adverse events experienced during the study that meet dose limiting toxicity criteria per the study protocol.

    Measured: First 4 weeks of treatment for each subject.

  4. Assess Overall Response Rate

    To assess the Overall Response Rate (ORR) per RECIST 1.1 criteria.

    Measured: Through 90 days after completion of the study, an average of 1 year.

Secondary outcomes (4)

  1. Serum concentrations of DF9001 will be determined at various time points.

    Concentration vs time of DF9001 will be measured using blood samples taken at various time points on study.

    Measured: From start of treatment up through 7 days after the decision to stop study treatment.

  2. Assess the best overall response (BOR) per RECIST v1.1.

    To assess Best Overall Response (BOR)

    Measured: Through 90 days after completion of the study, an average of 1 year.

  3. Assess the duration of response (DOR) per RECIST v1.1.

    To assess Duration of Response (DOR) of DF9001

    Measured: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months.

  4. Assess progression-free survival (PFS) for DF9001 per RECIST v1.1.

    To assess Progression Free Survival (PFS) for DF9001

    Measured: From time of initiation of therapy until the date of first documented tumor progression, assessed up to 24 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Oct 2022
  2. Study start15 Nov 2022
  3. Primary completion15 Aug 2025
  4. Study completion15 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05597839
Sponsor's protocol ID
DF9001-001
Other IDs
KEYNOTE-F92, MK-3475-F92
Status last verified
Oct 2025
First submitted
18 Oct 2022
Last updated
29 Oct 2025
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DF9001 and KEYTRUDA® (pembrolizumab) in people with Solid Tumor, Adult, run by Dragonfly Therapeutics at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 48 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number, severity, and duration of treatment-related adverse events (TRAEs) according to NCI-CTCAE v5.0. (time frame: Screening visit up to 28 days after last treatment on the study.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05597839.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2025.

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